INTRODUCTION

Section 2 of 11  

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Background

Myocardial infarction (MI) is the rapid development of myocardial necrosis caused by a critical imbalance between oxygen supply and demand of the myocardium. This usually results from plaque rupture with thrombus formation in a coronary vessel, resulting in an acute reduction of blood supply to a portion of the myocardium.

Although the clinical presentation of a patient is a key component in the overall evaluation of the patient with MI, many events are either "silent" or are clinically unrecognized, evidencing that patients and physicians often do not recognize symptoms of a MI. The appearance of cardiac markers in the circulation generally indicates myocardial necrosis and is a useful adjunct to diagnosis.

Cardiac markers help to categorize MI, which is considered part of a spectrum referred to as acute coronary syndrome that includes ST-elevation MI (STEMI), non–ST-elevation MI (NSTEMI), and unstable angina. This categorization is valuable because patients with ischemic discomfort may or may not have ST-segment elevations on their electrocardiogram. Those without ST elevations may ultimately be diagnosed with NSTEMI or with unstable angina based on the presence or absence of cardiac enzymes. Additionally, therapeutic decisions, such as administering an intravenous thrombolytic or performing percutaneous coronary intervention (PCI), are often made based on this categorization.

Pathophysiology

The most common cause of MI is narrowing of the epicardial blood vessels due to atheromatous plaques. Plaque rupture with subsequent exposure of the basement membrane results in platelet aggregation, thrombus formation, fibrin accumulation, hemorrhage into the plaque, and varying degrees of vasospasm. This can result in partial or complete occlusion of the vessel and subsequent myocardial ischemia. Total occlusion of the vessel for more than 4-6 hours results in irreversible myocardial necrosis, but reperfusion within this period can salvage the myocardium and reduce morbidity and mortality.

Nonatherosclerotic causes of MI include coronary vasospasm as seen in variant (Prinzmetal) angina and in patients using cocaine and amphetamines; coronary emboli from sources such as an infected heart valve; occlusion of the coronaries due to vasculitis; or other causes leading to mismatch of oxygen supply and demand, such as acute anemia from GI bleeding. MI induced by chest trauma has also been reported, usually following severe chest trauma such as motor vehicle accidents and sports injuries. For additional information, see Medscape's article "New Definition of 'MI' Poised for World Domination".

Frequency

United States

MI is a leading cause of morbidity and mortality in the United States. Approximately 1.3 million cases of nonfatal MI are reported each year, for an annual incidence rate of approximately 600 cases per 100,000 people. The proportion of patients diagnosed with NSTEMI compared with STEMI has progressively increased.

International

Cardiovascular diseases account for 12 million deaths annually worldwide. MI continues to be a significant problem in industrialized countries and is becoming an increasingly significant problem in developing countries.

Mortality/Morbidity

Approximately 500,000-700,000 deaths are caused by ischemic heart disease annually in the United States.

One third of patients who experience STEMI die within 24 hours of the onset of ischemia, and many of the survivors experience significant morbidity. For many patients, the first manifestation of coronary artery disease is sudden death likely from malignant ventricular dysrhythmia.

• More than one half of deaths occur in the prehospital setting.
• In-hospital fatalities account for 10% of all deaths. An additional 10% of deaths occur in the first year postinfarction.
• A steady decline has occurred in the mortality rate from STEMI over the last several decades. This appears to be due to a combination of a fall in the incidence of MI (replaced in part by an increase in the incidence of unstable angina) and a reduction in the case-fatality rate once an MI has occurred.

Sex

A male predilection exists in persons aged 40-70 years. Evidence exists that women more often have MIs without atypical symptoms. The atypical presentation in women might explain the sometimes delayed diagnosis of MIs in women.

In persons older than 70 years, no sex predilection exists.

Age

MI most frequently occurs in persons older than 45 years.

Certain subpopulations younger than 45 years are at risk, particularly cocaine users, persons with type 1 diabetes mellitus, patients with hypercholesterolemia, and those with a positive family history for early coronary disease. A positive family history includes any first-degree male relative aged 45 years or younger or any first-degree female relative aged 55 years or younger who experienced a myocardial infarction. In younger patients, the diagnosis may be hampered if the physician does not maintain a high index of suspicion.

CLINICAL

Section 3 of 11  

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History

The history is critical in making the diagnosis of MI and sometimes may provide the only clues that lead to the diagnosis in the initial phases of the patient presentation.

• Chest pain, usually across the anterior precordium is typically described as tightness, pressure, or squeezing.
• Pain may radiate to the jaw, neck, arms, back, and epigastrium. The left arm is more frequently affected; however, a patient may experience pain in both arms.
• Dyspnea, which may accompany chest pain or occur as an isolated complaint, indicates poor ventricular compliance in the setting of acute ischemia. Dyspnea may be the patient's anginal equivalent, and, in an elderly person or a patient with diabetes, it may be the only complaint.
• Nausea, abdominal pain, or both often are present in infarcts involving the inferior or posterior wall.
• Anxiety
• Lightheadedness with or without syncope
• Cough
• Nausea with or without vomiting
• Diaphoresis
• Wheezing
• Elderly patients and those with diabetes may have particularly subtle presentations and may complain of fatigue, syncope, or weakness. The elderly may also present with only altered mental status. Those with preexisting altered mental status or dementia may have no recollection of recent symptoms and may have no complaints whatsoever.
• As many as half of MIs are clinically silent in that they do not cause the classic symptoms described above and consequently go unrecognized by the patient. A high index of suspicion should be maintained for MI especially when evaluating women, patients with diabetes, older patients, patients with dementia, and those with a history of heart failure. Patients with a permanent pacemaker in place may confound recognition of STEMI by 12-lead ECG due to the presence of paced ventricular contractions.

Physical

The physical examination can often be unremarkable.

• Patients with ongoing symptoms usually lie quietly in bed and appear pale and diaphoretic.
• Hypertension may precipitate MI, or it may reflect elevated catecholamine levels due to anxiety, pain, or exogenous sympathomimetics.
• Hypotension may indicate ventricular dysfunction due to ischemia. Hypotension in the setting of MI usually indicates a large infarct secondary to either decreased global cardiac contractility or a right ventricular infarct.
• Acute valvular dysfunction may be present. Valvular dysfunction usually results from infarction that involves the papillary muscle. Mitral regurgitation due to papillary muscle ischemia or necrosis may be present.
• Rales may represent congestive heart failure.
• Neck vein distention may represent pump failure. With right ventricular failure, cannon jugular venous a waves may be noted.
• Third heart sound (S₃) may be present.
• A fourth heart sound is a common finding in patients with poor ventricular compliance that is due to preexisting heart disease or hypertension.
• Dysrhythmias may present as an irregular heartbeat or pulse.
• Low-grade fever is not uncommon.

Causes

The most frequent cause of MI is rupture of an atherosclerotic plaque within a coronary artery with subsequent arterial spasm and thrombus formation.

Other causes include the following:

• Coronary artery vasospasm
• Ventricular hypertrophy (eg, left ventricular hypertrophy [LVH], idiopathic hypertrophic subaortic stenosis [IHSS], underlying valve disease)
• Hypoxia due to carbon monoxide poisoning or acute pulmonary disorders (Infarcts due to pulmonary disease usually occur when demand on the myocardium dramatically increases relative to the available blood supply.)
• Coronary artery emboli, secondary to cholesterol, air, or the products of sepsis
• Cocaine, amphetamines, and ephedrine
• Arteritis
• Coronary anomalies, including aneurysms of the coronary arteries
• Increased afterload or inotropic effects, which increase the demand on the myocardium
• Aortic dissection, with retrograde involvement of the coronary arteries
• Although rare, pediatric coronary artery disease may be seen with Marfan syndrome, Kawasaki disease, Takayasu arteritis, progeria, and cystic medial necrosis (see Myocardial Infarction in Childhood).

Risk factors for atherosclerotic plaque formation include the following:

• Age
• Male gender
• Smoking
• Hypercholesterolemia and hypertriglyceridemia, including inherited lipoprotein disorders
• Diabetes mellitus
• Poorly controlled hypertension
• Type A personality
• Family history
• Sedentary lifestyle

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Biliary tract disease
Esophageal spasm
Gastroesophageal reflux disease
Unstable angina

WORKUP

Section 5 of 11  

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Lab Studies

• Troponin is the preferred biomarker for diagnosis.
• • Troponins have the greatest sensitivity and specificity in detecting MI. The test result is both diagnostic as well as prognostic of outcome.
  • Troponin is a contractile protein that normally is not found in serum. It is released only when myocardial necrosis occurs.
  • For early detection of myocardial necrosis, sensitivity of this laboratory test is superior to that of the creatine kinase-MB (CK-MB). Troponin I is detectable in serum 3-6 hours after an AMI and its level remains elevated for 14 days.
  • Troponin is also the optimum biomarker for the evaluation of patients with MI who have coexistent skeletal muscle injury.
• Creatine kinase–MB level  
• • CK-MB levels begin to rise within 4 hours after injury, peak at 18-24 hours, and subside over 3-4 days. A level within the reference range does not exclude myocardial necrosis.
  • Occasionally, very small infarcts can be missed by CK-MB; therefore, a troponin level should be measured for patients suspected of having had MI who have negative serial CK-MBs.
• Myoglobin levels  
• • Myoglobin, a low-molecular-weight heme protein found in cardiac and skeletal muscle, is released more rapidly from infarcted myocardium than troponin and CK-MB and may be detected as early as 2 hours after MI. Myoglobin levels rise early in the course of MI.
  • The marker has high sensitivity but poor specificity. When performed in conjunction with other studies, it may be useful for the early detection of MI.
• Complete blood count
• • CBC is indicated if anemia is suspected as a precipitant. Transfusion with packed red blood cells may be indicated.
  • Leukocytosis may be observed within several hours after an AMI. It peaks in 2-4 days and returns to levels within the reference range within 1 week.
• Chemistry profile
• • Potassium and magnesium levels should be monitored and corrected.
  • Creatinine levels must be considered before using an angiotensin-converting enzyme (ACE) inhibitor.
• C-reactive protein (CRP) is a marker of acute inflammation. Patients without biochemical evidence of myocardial necrosis but with elevated CRP level are at increased risk of a subsequent ischemic event.
• Erythrocyte sedimentation rate (ESR) rises above reference range values within 3 days and may remain elevated for weeks.
• Serum lactate dehydrogenase (LDH) level rises above the reference range within 24 hours of MI, reaches a peak within 3-6 days, and returns to the baseline within 8-12 days.

Imaging Studies

• Chest radiography
• • Chest radiography may provide clues to an alternative or complicating diagnosis (eg, aortic dissection, pneumothorax). Other imaging studies such as a contrast chest CT scan or transesophageal echocardiography should be used to differentiate MI from aortic dissection in patients in whom the diagnosis is in doubt. Stanford type A aortic dissections may dissect in a retrograde fashion causing coronary blockage and dissection, which may result in MI. In one study, 8% of patients with Stanford type A dissections had ST elevation on ECG.
  • Chest radiography also reveals complications of MI such as pulmonary edema secondary to heart failure.
• Echocardiography
• • Use 2-dimensional and M-mode echocardiography when evaluating wall motion abnormalities and overall ventricular function.
  • Echocardiography can identify complications of MI (eg, valvular insufficiency, ventricular dysfunction, pericardial effusion).
• Technetium-99m sestamibi scan
• • Technetium-99m is a radioisotope that is taken up by the myocardium in proportion to the blood flow and is only minimally redistributed after initial uptake. This allows for time delay between injection of the isotope and imaging.
  • It has potential use in identifying infarct in patients with atypical presentations or in patients with ECGs that are not interpretable.
  • Normal scan findings are associated with an extremely low risk of subsequent cardiac events.
• Thallium scanning: Thallium accumulates in the viable myocardium.
• Perfusion imaging has been used in risk stratification after MI and for measurement of infarct size to evaluate reperfusion therapies. Novel "hot spot" imaging radiopharmaceuticals that visualize infarction or ischemia are currently undergoing evaluation and hold promise for the future. (See Myocardial Ischemia - Nuclear Medicine and Risk Stratification.)
• Recent advances include dual-source 64-slice CT scanning that can do a full scan in 10 seconds and produce high-resolution images that allow fine details of the patient's coronary arteries to be seen. This technology allows for noninvasive and early diagnosis of coronary artery disease and thus earlier treatment before the coronary arteries become more or completely occluded. It allows direct visualization of not only the lumen of the coronary arteries but also plaque within the artery. Dual-source 64-slice CT scanning is being used with intravenous contrast to determine if a stent or graft is open or closed.
• MRI can identify wall thinning, scar, delayed enhancement (infarction), and wall motion abnormalities (ischemia). Currently, this is not a primary diagnostic modality for MI, but coronary artery assessment may be enhanced by magnetic resonance angiography (MRA) in the future.

Other Tests

• Electrocardiography
• • An ECG should be obtained as soon as possible after presentation to the ED.
  • Approximately one half of patients have diagnostic changes on their initial ECG.
  • Because the symptoms of AMI can be subtle or protean, an ECG should be performed on any patient who is older than 45 years and is experiencing any form of thoracoabdominal discomfort, including new epigastric pain or nausea.
  • In younger patients, an ECG should be considered when suggestive symptoms are present or in patients with risk factors for early coronary artery disease. Younger patients are disproportionately represented in missed cases. An ECG is a rapid, low-risk, relatively low-cost measure.
  • Results that indicate high probability of MI are ST-segment elevation greater than 1 mm in 2 anatomically contiguous leads or the presence of new Q waves.
  • Results that indicate intermediate probability of MI are ST-segment depression, T-wave inversion, and other nonspecific ST-T wave abnormalities.
  • Results that indicate low probability of MI are normal findings on ECG; however, normal or nonspecific findings on ECG do not exclude the possibility of MI.
  • Localization of MI based on distribution of ECG abnormalities is as follows:
  • • Inferior wall - II, III, aVF
    • Lateral wall - I, aVL, V₄  through V₆
    • Anteroseptal - V₁ through V₃
    • Anterolateral - V₁ through V₆
    • Right ventricular - RV₄, RV₅
    • Posterior wall - R/S ratio >1 in V₁ and V₂; T-wave changes (ie, upright) in V₁, V₈, and V₉

Procedures

• Percutaneous coronary interventions (PCIs) are a group of catheter-based technologies used to establish coronary reperfusion. Angiography provides essential knowledge of the extent of coronary disease and is performed prior to PCI. PCI may then be performed as a primary intervention or as an intervention after thrombolysis failure. Evidence suggests that primary PCI is more effective than thrombolysis and should be performed for confirmed STEMI, new or presumably new left bundle-branch block (LBBB), severe congestive heart failure, or pulmonary edema if it can be performed within 12 hours of symptom onset. Door-to-balloon time should be 90 minutes or less.
• • Percutaneous transluminal coronary angioplasty (PTCA) (balloon angioplasty) is the primary therapeutic modality used at centers where it can provide reperfusion as quickly as fibrinolytic therapy. In other centers, it is used selectively for patients failing to respond to thrombolytics.
  • PCI has fewer bleeding complications and recurrent ischemia when compared with thrombolysis. PCI restores coronary artery patency in more than 90% of patients.
  • A drawback of PCI is the need for 24-hour availability of an angioplasty suite with the required staff and the availability of backup cardiothoracic capabilities. Primary PCI for STEMI should be performed at hospitals with readily available cardiothoracic surgery. Readily available may be defined as the ability to transport patients quickly to a hospital with cardiothoracic capabilities.
• Coronary artery bypass graft may be indicated based on angiographic findings.
• Morbidity and mortality from MI are significantly reduced if patients and bystanders recognize symptoms early, activate the EMS system, and thereby shorten the time to definitive treatment. Trained prehospital personnel can provide life-saving interventions if the patient develops cardiac arrest. The key to improved survival is the availability of early defibrillation. Approximately 1 in every 300 patients with chest pain transported to the ED by private vehicle goes into cardiac arrest en route. Several studies have confirmed that patients with STEMI usually do not call 911; in one study, only 23% of patients with a confirmed coronary event used EMS.

TREATMENT

Section 6 of 11  

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Prehospital Care

• All patients being transported for chest pain should be managed as if the pain were ischemic in origin unless clear evidence to the contrary is established.
• If available, an ALS unit should transport patients with hemodynamic instability or respiratory difficulty.
• Prehospital notification by Emergency Medical Services (EMS) personnel should alert ED staff to the possibility of a patient with MI. EMS personnel should receive online medical advice for a patient with high-risk presentation.
• The American Heart Association (AHA) protocol can be adopted for use by prehospital emergency personnel. This protocol recommends empirical treatment of patients with suspected STEMI with morphine, oxygen, nitroglycerin, and aspirin.
• Specific prehospital care includes the following:
• • Intravenous access, supplemental oxygen, pulse oximetry
  • Immediate administration of aspirin en route
  • Nitroglycerin for active chest pain, given sublingually or by spray
  • Telemetry and prehospital ECG, if available
• EMS protocol should be formulated to strongly consider taking patients with suspected MI/ACS, and certainly patients with STEMI, to facilities capable of PCI if geographically possible.
• Prehospital thrombolysis allows eligible patients to receive thrombolysis 30-60 minutes sooner than if treatment were given in the ED; however, prehospital thrombolysis is still under investigation.

Emergency Department Care

For purposes of determining appropriate treatment, viewing MI as part of a spectrum of coronary syndromes is helpful; this spectrum includes (1) STEMI, (2) NSTEMI, and (3) unstable angina. Patients with persistent ST elevation should be considered for reperfusion therapy (thrombolysis or primary PCI.) Those without ST elevation will be diagnosed with either NSTEMI if cardiac marker levels are elevated or with unstable angina if serum cardiac marker levels provide no evidence of myocardial injury. Patients presenting with no ST-segment elevation are not candidates for immediate thrombolytics but should receive anti-ischemic therapy and may be candidates for PCI urgently or during admission. Confirmation of the diagnosis of NSTEMI requires waiting for the results of cardiac markers. In the case of unstable angina, diagnosis may await further diagnostic studies such as coronary angiography or imaging studies to confirm the diagnosis and to distinguish it from noncoronary causes of chest pain.

The initial focus should be on identifying patients with STEMI. An ECG should be performed and shown to an experienced emergency medicine physician within 10 minutes of ED arrival. If STEMI is present, the decision as to whether the patient will be treated with thrombolysis or primary PCI should be made within the next 10 minutes. The goal for patients with STEMI should be to achieve a door-to-drug time of within 30 minutes and a door-to-balloon time of within 90 minutes. If STEMI is not present, then the workup should proceed looking for unstable angina or NSTEMI and for alternative diagnoses.

Treatment is aimed at (1) restoration of the balance between the oxygen supply and demand to prevent further ischemia, (2) pain relief, and (3) prevention and treatment of complications.

• Delays in administration of thrombolysis often occur because of delay in obtaining an ECG, interpretation, lack of immediate availability of thrombolytic agents, and outdated protocols requiring cardiology consultation before thrombolytic treatment.
• An ECG should be performed as soon as possible after the patient presents to the ED. The ECG should be hand-delivered to an experienced physician for timely review.
• All patients should be placed on telemetry.
• Two large-bore IVs should be inserted if the EMS has not already completed this.
• Pulse oximetry should be performed, and appropriate supplemental oxygen should be given (maintain oxygen saturation >90%).
• A chest radiograph should be obtained soon after arrival to screen for alternative causes of chest pain and identify possible contraindications to thrombolysis (eg, aortic dissection).
• Pharmacologic intervention is likely to include the following:
• • Aspirin should be administered immediately if not already taken by the patient at home or administered by EMS before arrival. Aspirin has been shown to decrease mortality and reinfarction rates after MI. Use clopidogrel (Plavix) in case of aspirin allergy.
  • Beta-blocker therapy for heart rate control and resultant decrease of myocardial oxygen demand if not contraindicated. Metoprolol (Lopressor) is the standard and is a selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. Beta-blockers reduce the rates of reinfarction and recurrent ischemia and may also reduce mortality.
  • Morphine sulphate may be administered for relief of pain and anxiety.
• Nitrates are useful for preload reduction and symptomatic relief but have no apparent impact on mortality rate in MI. Systolic BP <90, HR <60 or >100, and RV infarction are a contraindications to nitrate use. Intravenous nitroglycerin is indicated for relief of ongoing ischemic discomfort, control of hypertension, or management of pulmonary congestion. Nitrates should not be administered to patients who have taken any phosphodiesterase inhibitor for erectile dysfunction within the last 24 hours (extend timeframe to 48 h for tadalafil).
• Thrombolytic therapy has been shown to improve survival rates in MI.
• • Door-to-drug time should be no more than 30 minutes. Thrombolytic therapy administered within the first 2 hours can occasionally abort MI and dramatically reduce the mortality rate.
  • The optimal approach is to administer thrombolytics as soon as possible after onset of symptoms (up to 12 h from symptom onset according to some authors) in patients with ST-segment elevation greater than 1 mm in 2 or more anatomically contiguous ECG leads, new or presumed new left bundle-branch block, or anterior ST depression where posterior infarction is suspected. With ST-segment elevation, the diagnosis is relatively secured; therefore, initiation of reperfusion therapy should not be delayed for the results of cardiac markers.
  • Thrombolysis is generally preferred to PCI in cases where the time from symptom onset is less than 3 hours and if there would be a delay to PCI, greater than 1-2 additional hours to door-to-balloon time. A detailed list of contraindications and cautions for the use of fibrinolytic therapy is shown in Table 12 of the ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction—Executive Summary, at the American College of Cardiology.
• Administer a platelet glycoprotein (GP) IIb/IIIa-receptor antagonist (eptifibatide, tirofiban, or abciximab), in addition to aspirin and unfractionated heparin, to patients with continuing ischemia or with other high-risk features and to patients in whom PCI is planned. Studies suggest that the addition of intravenous platelet glycoprotein (GP) IIb/IIIa-receptor antagonists to aspirin and heparin improves both early and late outcomes, including mortality, Q-wave MI, need for revascularization procedures, and length of hospital stay.
• Despite the traditional use of unfractionated heparin in ST elevation MI for decades, controversy regarding its role continues.
• • In patients treated with fibrinolytic therapy, recommendations for heparin therapy depend on the fibrinolytic agent. Heparin has an established role as an adjunctive agent in patients receiving alteplase, reteplase, or tenecteplase but should not be used with nonselective fibrinolytic agents such as streptokinase and anistreplase.
  • Heparin is also indicated in patients undergoing primary PCI. Data are scant with regard to heparin efficacy in patients not receiving thrombolytic therapy in the setting of MI; however, considerable rationale exists for ancillary heparin therapy to inhibit the coagulation cascade.
  • Low-molecular-weight heparins (LMWH) are commonly used because of convenient dosing and reliable therapeutic levels, but there have been no definitive trials of LMWH in patients with STEMI to provide a firm basis for recommendations. Low-molecular-weight heparin should not be used as an alternative to unfractionated heparin as ancillary therapy to fibrinolytics in patients aged older than 75 years or in patients with significant renal dysfunction (serum creatinine level >2.5 mg/dL in men or >2 mg/dL in women).
• An ACE inhibitor (Captopril) should be given orally within the first 24 hours of STEMI to patients with anterior infarction, pulmonary congestion, or left ventricular ejection fraction (LVEF) less than 40% in the absence of hypotension.
• An angiotensin receptor blocker (valsartan or candesartan) should be administered to patients with STEMI who are intolerant of ACE inhibitors and who have either clinical or radiological signs of heart failure or LVEF less than 40%.
• Note that routine use of lidocaine as prophylaxis for ventricular arrhythmias in patients who have experienced an MI has been shown to increase mortality rates and its use is class indeterminate.
• Use of calcium channel blockers in the acute setting has come into question, with some randomized controlled trials and retrospective studies showing increased adverse effects. Diltiazem and verapamil should be avoided in patients with pulmonary edema or severe left ventricular (LV) dysfunction.

Consultations

Great differences in practice patterns and treatment outcomes exist in different hospital and geographic areas. This is due, at least in part, to the wide variation in the availability of PCI and emergency thoracotomy. One study showed that transferring patients to an invasive-treatment center for PCI is superior to on-site fibrinolysis provided that the transfer can be accomplished within 2 hours. Methods used for reperfusion/revascularization must be based on the resources available in a particular community, and protocols should be worked out in advance as a collaborative effort between emergency physicians, internists, cardiologists, and cardiothoracic surgeons.

• The decision to administer a thrombolytic agent may be made by the emergency physician, with or without the input of a cardiologist, depending on institutional protocol. In a center with the full range of treatment options, an expeditious phone consultation with a cardiologist would seem to be a wise choice to ascertain that the best possible option is chosen for the patient.
• A cardiologist should be consulted for the following:
• • Patients who may benefit from PCI, including "rescue PCI," with transfer if required, for patients in whom thrombolysis for STEMI fails to achieve reperfusion
  • Patients in cardiogenic shock
  • Patients with hemodynamically significant new or worsening murmur
  • Patients who are not candidates for thrombolytic intervention because of a contraindication
  • Intractable angina despite medications
  • Severe pulmonary congestion
  • Late presentation (>3 h but no more than 12 h)
  • Where the diagnosis is in doubt
  • Note that PCI door-to-balloon time should be less than 90 minutes.
  • Thoracotomy for coronary artery bypass graft may be indicated if PCI fails. Thoracotomy may also be necessary for valvular repair or in cases of mechanical complications such as LV rupture.

MEDICATION

Section 7 of 11  

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The main goals of ED medical therapy are rapid intravenous thrombolysis and/or rapid referral for PCI, optimizing oxygenation, decreasing cardiac workload, and controlling pain.

Drug Category: Antithrombotic agents

These agents prevent the formation of thrombus associated with myocardial infarction and inhibit platelet function by blocking cyclooxygenase and subsequent aggregation. Antiplatelet therapy has been shown to reduce mortality rates by reducing the risk of fatal myocardial infarctions, fatal strokes, and vascular death.

Drug Name	Heparin
Description	Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse preformed clot, but it is able to inhibit further thrombogenesis after thrombolysis. Heparin should be administered to patients undergoing PCI. Prevents reaccumulation of clot after spontaneous fibrinolysis. Benefit as adjunctive therapy for streptokinase not clear.
Adult Dose	60 U/kg (max 4000 U) IV bolus; followed by a 12 U/kg/h (max 1000 U/h) maintenance infusion
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; subacute bacterial endocarditis, active bleeding; history of heparin-induced thrombocytopenia
Interactions	Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase heparin toxicity
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Caution in severe hypotension and shock

Drug Name	Enoxaparin (Lovenox)
Description	Produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). LMWH differs from UFH by having a higher ratio of antifactor Xa to antifactor IIa compared with UFH. Binds to antithrombin III, enhancing its therapeutic effect. The heparin-antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin). Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis. Advantages include intermittent dosing and decreased requirement for monitoring. Heparin anti–factor Xa levels may be obtained if needed to establish adequate dosing. No utility in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect). Indicated for treatment of acute ST-segment elevation myocardial infarction (STEMI) managed medically or with subsequent percutaneous coronary intervention (PCI). Also indicated as prophylaxis of ischemic complications caused by unstable angina and non-Q-wave MI.
Adult Dose	Treatment regimens include aspirin (75-325 mg/d) if not contraindicated NSTEMI 1 mg/kg SC bid CrCl <30 mL/min: 1 mg/kg SC qd STEMI <75 years: 30 mg IV single bolus plus 1 mg/kg SC, then 1 mg/kg SC q12h; not to exceed 100 mg/dose for first 2 SC doses <75 years and CrCl <30 mL/min: 30 mg IV single bolus plus 1 mg/kg SC, then 1 mg/kg SC qd; not to exceed 100 mg/dose for first 2 SC doses >75 years: 0.75 mg/kg SC q12h (no initial IV bolus administered), not to exceed 75 mg/dose for first 2 doses >75 years and CrCl <30 mL/min: 1 mg/kg SC qd (no initial IV bolus administered) With PCI: If last enoxaparin dose administered >8 h before balloon inflation, administer an additional IV bolus of 0.3 mg/kg With thrombolytic agent: Give dose specified for age and renal function between 15 min before and 30 min after the start of fibrinolytic therapy
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; major bleeding; thrombocytopenia
Interactions	Platelet inhibitors or oral anticoagulants such as dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, and ticlopidine may increase risk of bleeding
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Decrease dose if CrCl <30 mL/min; if thromboembolic event occurs despite LMWH prophylaxis, discontinue drug and initiate alternate therapy; elevation of hepatic transaminase levels may occur but is reversible; heparin-associated thrombocytopenia may occur with fractionated low-molecular-weight heparins; 1 mg of protamine sulfate reverses effect of approximately 1 mg of enoxaparin if significant bleeding complications develop; cases of epidural/spinal hematomas have been reported in adults receiving spinal or epidural anesthesia (holding 2 doses prior to LP or surgery is recommended); obtain hemostasis at puncture site before sheath removal after PCI

Drug Category: Vasodilators

These agents oppose coronary artery spasm, which augments coronary blood flow and reduces cardiac work by decreasing preload and afterload. It is effective in the management of symptoms in AMI and has no apparent impact on mortality rate. Nitroglycerin can be administered sublingually by tablet or spray, topically, or intravenously. In the setting of AMI, topical administration is a less desirable route because of unpredictable absorption and onset of clinical effects.

Drug Category: Beta-adrenergic blockers

These agents inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation and reduce blood pressure, which decreases myocardial oxygen demand. Short-term and long-term mortality rates are reduced in patients with AMI. Greatest benefit is achieved when given within 8 hours of symptom onset. Aim for a target heart rate of 60-90 beats per minute.

Drug Name	Esmolol (Brevibloc)
Description	Excellent drug for use in patients at risk for complications from beta-blockade, particularly those with reactive airway disease, mild-to-moderate LV dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if needed.
Adult Dose	Loading dose: 500 mcg/kg/min IV over 1 min Optional loading dose: 0.5 mg/kg slow IV infusion Maintenance dose: 0.1 mg/kg/min IV initially; titrate in increments of 0.05 mg/kg/min q10-15min to a total dose of 0.2 mg/kg/min Average maintenance dose: 50 mcg/kg/min IV over 4 min
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; uncompensated congestive heart failure; bradycardia; cardiogenic shock; AV conduction abnormalities; cocaine-related ischemia
Interactions	Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of esmolol, possibly resulting in decreased pharmacologic effect; cardiotoxicity of esmolol may increase when administered concurrently with sparfloxacin, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives; toxicity of esmolol increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm may worsen when medication is abruptly withdrawn (withdraw drug slowly and monitor patient closely); caution in patients on other negative inotropes, such as verapamil

Drug Category: Thrombolytic agents

These agents prevent recurrent thrombus formation and rapid restoration of hemodynamic disturbances. In addition, they remove pathologic intraluminal thrombus or embolus not yet dissolved by the endogenous fibrinolytic system. When given within 12 h of symptom onset, they restore patency of occluded arteries, salvage myocardium, and reduce morbidity and mortality rates of AMI. Thrombolytic treatment should be started within 30 min of arrival (door-drug time). Maximum benefit occurs when administered within 1-3 h of symptom onset.

Drug Name	Tenecteplase (TNKase)
Description	Modified version of alteplase (tPA) made by substituting 3 amino acids of alteplase. Can be given as single bolus over 5-second infusion instead of 90 min with alteplase. Appears to cause less nonintracranial bleeding but has similar risk of intracranial bleeding and stroke as alteplase. Base the dose using patient weight. Initiate treatment as soon as possible after onset of AMI symptoms. Because tenecteplase contains no antibacterial preservatives, reconstitute immediately before use.
Adult Dose	Give IV bolus over 5 s using body weight; not to exceed 50 mg <60 kg: 30 mg (6 mL) 60-70 kg: 35 mg (7 mL) 70-80 kg: 40 mg (8 mL) 80-90 kg: 45 mg (9 mL) >90 kg: 50 mg (10 mL)
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; active internal bleeding; intracranial neoplasm; known bleeding diathesis; severe uncontrolled hypertension; arteriovenous malformation or aneurysm; history of stroke; intracranial or intraspinal surgery or trauma within 2 mo
Interactions	Heparin and vitamin K antagonists, acetylsalicylic acid, dipyridamole, and GP IIb/IIIa inhibitors may increase risk of bleeding if coadministered with tenecteplase therapy
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Caution if readministering to patients who have received prior plasminogen activator therapy (may develop immunity); coronary thrombolysis may result in arrhythmias associated with reperfusion but not different from those often observed in ordinary course of AMI (may be managed with standard antiarrhythmic measures); in elderly patients, weigh benefits of tenecteplase on mortality against risk of increased adverse events, including bleeding; cholesterol embolism is associated with all types of thrombolytic agents but true incidence is unknown

Drug Name	Anistreplase (Eminase)
Description	Recently approved for use in AMI. Nonfibrin specific agent with a half-life of 90 min. Activates the conversion of plasminogen to plasmin, which is capable of degrading fibrin, fibrinogen, and other procoagulant proteins into soluble fragments. These effects result in thrombolysis. Has no survival benefit over streptokinase and higher rate of allergic and bleeding complications. Easier to administer than tPA, has a lower cost ($1500), and does not require heparinization.
Adult Dose	30 U IV over 2-5 min
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; history of stroke; intracranial neoplasm; active internal bleeding; recent intracranial surgery; severe uncontrolled hypertension; arteriovenous malformation or aneurysm
Interactions	Increases bleeding potential of heparin, warfarin, and aspirin
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Caution in cardiovascular arrhythmias, hypotension, and perfusion arrhythmias

Drug Name	Streptokinase (Kabikinase, Streptase)
Description	Nonfibrin specific agent with a half-life of 23 min. Need for adjunctive therapy with heparin is controversial. Acts with plasminogen to convert plasminogen to plasmin. Plasmin degrades fibrin clots as well as fibrinogen and other plasma proteins. An increase in fibrinolytic activity that degrades fibrinogen levels for 24-36 h takes place with intravenous infusion of streptokinase.
Adult Dose	1.5 million U in 50 mL D5W IV over 60 min
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; active internal bleeding; intracranial neoplasm; aneurysm; diathesis; severe uncontrolled arterial hypertension
Interactions	Antifibrinolytic agents may decrease effects of streptokinase; heparin, warfarin, and aspirin may increase risk of bleeding
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Caution in severe hypertension, intramuscular administration of medications, and trauma or surgery in previous 10 d; measure hematocrit, platelet count, aPTT, TT, PT, or fibrinogen levels before therapy is implemented; either TT or aPTT should be less than twice the reference range control value following infusion of streptokinase and before (re)instituting heparin; PT, aPTT, TT or fibrinogen should be monitored 4 h after initiation of therapy

Drug Category: Platelet aggregation inhibitors

These agents inhibit platelet aggregation and reduce mortality.

Drug Name	Eptifibatide (Integrilin)
Description	Antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor, which reversibly prevents von Willebrand factor, fibrinogen, and other adhesion ligands from binding to the GP IIb/IIIa receptor. End effect is the inhibition of platelet aggregation. Effects persist over duration of maintenance infusion and are reversed when infusion ends.
Adult Dose	180 mcg/kg IV load; followed by 2 mcg/kg/min IV for 72 h PTCA: 135 mcg/kg IV bolus before procedure, followed by 0.5 mcg/kg/min IV for 20-24 h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severe hypertension (SBP >200 mm Hg), active internal bleeding, history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation or aneurysm, acute pericarditis or bleeding diathesis; trauma or stroke within previous 30 d; platelet count <100,000/mm3; history of thrombocytopenia following prior exposure to this product; serum creatinine level >2 mg/dL (for the 180-mcg/kg bolus and 2-mcg/kg/min infusion) or >4 mg/dL (for the 135-mcg/kg bolus and 0.5-mcg/kg/min infusion)
Interactions	Coadministration with heparin, warfarin, or aspirin may increase risk of bleeding; monitor closely when using other drugs that affect hemostasis
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in platelet count <150,000/mm3 and hemorrhagic retinopathy; caution with concurrent use of drugs that affect hemostasis, such as thrombolytics, ticlopidine, NSAIDs, warfarin, dipyridamole, and clopidogrel; measure activated clotting time (ACT) and maintain aPTT between 50-70 s unless a PCI needs to be performed; maintain ACT between 300-350 s during a PCI; if platelets decrease to <100,000/mm3, perform additional platelet counts to exclude possibility of pseudothrombocytopenia; if thrombocytopenia is confirmed, discontinue GP IIb/IIIa inhibitors and heparin and appropriately monitor and treat the condition; monitor aPTT 6 h after start of heparin infusion and adjust to maintain aPTT higher than twice the baseline level

Drug Name	Tirofiban (Aggrastat)
Description	Antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor that reversibly prevents von Willebrand factor, fibrinogen, and other adhesion ligands from binding to the GP IIb/IIIa receptor, thereby inhibiting platelet aggregation. Effects persist over the duration of maintenance infusion and are reversed after stopping the infusion.
Adult Dose	0.4 mcg/kg/min IV for 30 min; followed by 0.1 mcg/kg/min
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; history of intracranial hemorrhage; severe hypertension (SBP >200 mm Hg), active internal bleeding, intracranial neoplasm, arteriovenous malformation or aneurysm, acute pericarditis and bleeding diathesis; trauma or stroke within previous 30 d; platelet count <100,000/mm3, history of thrombocytopenia following prior exposure to this product; serum creatinine level >2 mg/dL (for the 180-mcg/kg bolus and 2-mcg/kg/min infusion) or >4 mg/dL for the 135-mcg/kg bolus and the 0.5-mcg/kg/min infusion
Interactions	Coadministration with heparin, warfarin, and aspirin may increase risk of bleeding
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in platelet count <150,000/mm3 and hemorrhagic retinopathy; caution with concurrent use of drugs that affect hemostasis, such as thrombolytics, ticlopidine, NSAIDs, warfarin, dipyridamole, and clopidogrel; measure activated clotting time (ACT) and maintain aPTT between 50-70 s unless a PCI needs to be performed; maintain ACT between 300-350 s during a PCI; if platelets decrease to <100,000/mm3, perform additional platelet counts to exclude possibility of pseudothrombocytopenia; if thrombocytopenia is confirmed, discontinue GP IIb/IIIa inhibitors and heparin, and appropriately monitor and treat condition; monitor aPTT 6 h after start of heparin infusion and adjust to maintain aPTT higher than twice baseline level

Drug Name	Abciximab (ReoPro)
Description	Chimeric human-murine monoclonal antibody approved for use in elective/urgent/emergent PCI. Binds to receptor with high affinity and reduces platelet aggregation by 80% for as long as 48 h following infusion. Prevents acute cardiac ischemic complications in unstable angina unresponsive to conventional therapy.
Adult Dose	0.25 mg/kg IV bolus, followed by 10 mcg/min IV for 12 h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; bleeding diathesis; thrombocytopenia (<100,000 cells/mcL); recent trauma; intracranial tumor; severe uncontrolled hypertension; history of vasculitis; stroke within 2 y
Interactions	Toxicity increases with coadministration of anticoagulants, antiplatelets, and thrombolytics
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Bleeding complications may occur in patients <75 kg body weight, >65 years, with history of GI disease, or who recently received thrombolytic therapy; severe thrombocytopenia may occur within first 24 h of use

Drug Category: Analgesics

These agents reduce pain, which decreases sympathetic stress. They may provide some preload reduction. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who experience chest discomfort resulting from a myocardial infarction.

Drug Category: Angiotensin-converting enzyme (ACE) inhibitors

These agents prevent conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, causing lowered aldosterone secretion.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• All patients with known or suspected MI should be admitted to an ICU.
• Patients should continue to receive beta-blockers, nitrates, and heparin, as indicated.
• ACE inhibitors have been shown to improve survival rates in patients who have experienced an MI. In the acute setting, afterload reduction from ACE inhibitors may reduce the risk of CHF and sudden death.
• Lidocaine may be indicated for patients with ventricular ectopy that is complex or for patients with hemodynamically significant, nonsustained, or sustained ventricular tachycardia. Recall that the routine use of lidocaine as prophylaxis for ventricular arrhythmias is contraindicated.

Transfer

• A recent study showed that the transfer of patients to an invasive-treatment center for primary PCI is superior to on-site fibrinolysis provided that the transfer can be accomplished within 2 hours. Transfer should be considered for those patients who are likely to benefit from PCI or cardiac surgery but who are in an institution where access to such interventions is not immediate. The benefits of transferring such a patient must outweigh the risks. Patients for whom transfer might be considered include the following:
• • Patients with new or worsening hemodynamically significant mitral regurgitant murmurs
  • Patients with known or suspected critical aortic stenosis and either ongoing ischemia or hemodynamic instability
  • Patients who have received thrombolysis and fail to reperfuse
  • Patients with significant LV dysfunction or cardiogenic shock

Deterrence/Prevention

• Patients should avoid risk factors when possible and act upon treatable risk factors.
• Seeking medical attention or calling 911 with the first symptoms or signs of angina may initiate the cascade of interventions that will ultimately prevent or limit damage to the myocardium. All patients should be educated as to these symptoms and signs and when to call 911.
• Daily low-dose aspirin may be helpful, but the decision to prescribe aspirin as a preventative measure for MI must be made by the patient's physician(s) considering his or her overall condition and risk-benefit ratio.

Complications

• Monitoring and treatment of arrhythmias and conduction disturbances are an important part of the treatment of a post-MI patient within the first 48 hours. Conduction disturbances are most commonly observed in inferior MI but are more ominous when they occur with anterior MI.
• Tachyarrhythmia
• • Sinus tachycardia is a poor prognostic sign that is indicative of ventricular dysfunction or failure.
  • PVCs - Simple (ie, <10/h), no need to treat
  • PVCs - Complex, NSVT/VT, lidocaine DOC
  • Accelerated idioventricular rhythm (AIVR) is the most common reperfusion arrhythmia, but it usually is well tolerated and does not require treatment.
• Bradyarrhythmia
• • Type I second-degree heart block (ie, Wenckebach) is associated with inferior wall MI. Treat using temporary pacing or atropine only if it is hemodynamically significant.
  • Type II second-degree heart block is associated with anterior wall MI and may require a permanent pacemaker. Bundle branch blocks (BBB) that are new or preexisting with new second-degree heart block may also mandate consideration for a permanent pacemaker.
• Cardiogenic shock
• • In the setting of an MI, cardiogenic shock is associated with an 80% in-hospital mortality rate.
  • Patients should undergo thrombolysis or PCI, placement of an intra-aortic balloon pump, or CABG.
• Valvular insufficiency
• • This may occur acutely when ischemia or an infarct of the papillary muscle occurs resulting in mitral regurgitation. It usually presents as flash pulmonary edema and hypotension. Papillary muscle rupture may require valve repair.
  • Ischemia often responds to medical therapy and thrombolysis.
• Congestive heart failure can be due to systolic or diastolic dysfunction in MI. The severity of the heart failure and systolic dysfunction depends on the extent of the infarct and the presence of any other complications, such as acute mitral regurgitation. Treatment may include nitrates, morphine, diuretics, and ACE inhibitors. Digoxin has no role in acute CHF due to ischemia.
• Right ventricular infarct occurs in the setting of an inferior wall infarction. Because patients with an RV infarct are preload-dependent, they often are identified by profound hypotension with normal pulmonary auscultation, particularly after nitroglycerin therapy. They respond to volume loading. This can be diagnosed by ST-segment elevation in right-sided chest leads (ie, V₄R, V₅R).
• Ventricular rupture occurs in the interventricular septum or the left ventricle free wall. Rupture represents a catastrophic event with mortality rates greater than 90%. Prompt recognition, stabilization, and surgical repair are crucial to any hope of survival. An echocardiogram usually defines the abnormality, and a right heart catheterization may show an oxygenation increase with septal rupture. It is more common in women, patients with hypertension, and those receiving NSAIDs or steroids.
• Other complications include pericarditis, ventricular aneurysm, and mural thrombus.

Prognosis

• MI may be associated with a mortality rate as high as 30%, with more than half of deaths occurring in the prehospital setting. Prognosis is highly variable and depends on a number of factors related to the timing and nature of intervention, success of the intervention (ie, infarct size), and post-MI management.
• Better prognosis is associated with factors including the following:
• • Successful early reperfusion
  • Preserved LV function
  • Short-term and long-term treatment with beta-blockers, aspirin, and ACE inhibitors
• Poorer prognosis is associated with the following:
• • Delayed or unsuccessful reperfusion
  • LV function is the strongest predictor of outcome in the post-MI patient.
• Ventricular dysrhythmias
• • Recent experience with amiodarone suggests that it may improve long-term mortality in survivors of MI with ectopy and ventricular tachycardia.

Patient Education

• For excellent patient education resources, see eMedicine's <